It has great power for research in the lab and there are hypothetical transformative clinical applications of CRISPR too. The latter efforts could include experimental attempts at reversal of disease-causing mutations in one-cell embryos with the hope that they then grow into full-fledged, healthy human beings. Hypothetically CRISPR could also be used for pursuing human enhancement via germline genetic modification.

As a tool CRISPR is exciting and my own lab is using it for genetic studies, but from a technical perspective it’s not perfect. It can introduce a range of types of errors into the genome, with largely unknown biological consequences. To date, the first and only reportof CRISPR-based modification of human embryos was arguably most notable for the problems encountered including genetic errors. However, suboptimal CRISPR methods were used so better design would almost certainly reduce risks of errors.

CRISPR raises a number of questions and has sparked many discussions. How should we handle a cutting edge biotechnology of this kind as a community of scientists? What if anything should be the appropriate role of others in such considerations including bioethicists? Should there be a temporary moratorium on clinical use of CRISPR? I tackled some of these issues in my own past piece Practical Plan for Managing Human Germline Genetic Modification. Others advocate for a more liberal perspective on the road to possible clinical use of CRISPR, focusing on the potential for great benefits.

Overall, this all might be summed up as follows: how do we balance the gas pedal and the brakes on CRISPR’s use in humans to aim for the greatest overall net benefit?

Professor Steven Pinker of Harvard has been one of the most outspoken advocates for more gas and less brakes here. Both in writing and in talks he has expressed the view that we should move forward without substantial impediments to CRISPR-Cas9. For instance, Pinker’s “get out of the way” editorial last week in TheBoston Globe on CRISPR was very critical of bioethics and advocated an expeditious path forward for the research without constraints. It sparked wide-ranging discussions and even some anger from bioethicists. Update: see also this brief replyto Pinker’s interview from noted bioethicist, Art Caplan.

A few days ago I reached out to Dr. Pinker to do an interview to learn more of the specifics about his views with a goal toward increasing dialogue. For instance, I wondered if he really felt that strongly about the harms caused by bioethics that were suggested in his editorial. I want to thank him for taking the time to provide such detailed answers that make the full depth of his views on these issues far clearer here than in the past.

Knoepfler. 1. Related to your talk at BEINGS and your more recent editorial, what do you see as the appropriate role for bioethics and bioethicists in the life sciences? “Get out of the way” seems rather absolute. Can you help us understand the nuances there in your view of bioethics if any?

Pinker: There’s a difference between ethics, on the one hand, and “bioethics” and “bioethicists,” on the other. Of course everything a scientist does—everything a human being does—ought to be ethically guided. But bioethics has become a professional guild that all too often impedes sound ethical concerns rather than advancing them. Many moral philosophers—the scholars who specialize in evaluating the soundness of ethical arguments—believe that mainstream bioethics commonly trades in confused claims based on emotion and woolly thinking (see these articles by Julian Savulescu, Sally Satel, and me for examples).

Take the very foundation of ethics. You’d think it would be an obvious ethical principle that life is better than death, health is better than disease, and vigor is better than disability. But, astonishingly, so-called bioethicists have repeatedly denied these truisms, either explicitly (in the case of the country’s former bioethicist-in-chief, Leon Kass, who argued that the desire to extend life is a sign of shallowness and immaturity), or implicitly, by fetishizing sweeping rubrics such as dignity, equity, social justice, sacredness, privacy, and consent at the expense of the health and lives of actual people.

It’s not just that many bioethicists practice bad moral philosophy. It’s that they are entangled in a conflict of interest. Institutionalized bioethics has become an academic and bureaucratic industry, and they need to rationalize their existence. You hardly need a bioethicist to tell you that it’s wrong to inject typhus into twins or to withhold antibiotics from syphilis patients. But to come up with an abstruse argument as to why a parent should be prohibited from saving the life of her infant by donating a part of her liver—for that you need a “bioethicist.”

Regarding my advice to “get out of the way,” the nuances were stated, albeit tersely, in the article. The first is that a truly ethical bioethics must weigh the benefits of any restriction on research against the harm that will be caused to the vast number of people who would benefit if the research proceeded expeditiously. Savulescu puts it starkly: “To delay by 1 year the development of a treatment that cures a lethal disease that kills 100,000 people per year is to be responsible for the deaths of those 100,000 people, even if you never see them.”

The second is that a truly ethical bioethics should justify any restrictions on research with rigorous, defensible arguments about benefit and harm, not with moralistic grandstanding, science fiction dystopias, perverse analogies to Nazis and nuclear weapons, esoteric theories pulled out of the air, or freak-show scenarios like armies of cloned Hitlers, people selling their eyeballs on eBay, or warehouses of zombies to supply people with spare organs—all of which I’ve heard in these debates.

And as I wrote, no one questions the need to protect patients and research subjects from exploitation or harm. If there are flaws in the existing safeguards, as, for example, Alice Dreger argues, the safeguards should be fine-tuned or re-engineered. This is not the same as giving more power to the bioethocrats. A great deal of bioethical argumentation has nothing to do with protecting people. It rather cooks up reasons why consenting adults should be prohibited from doing things that help them or others while harming no one—a prominent example being recipient-solicited or incentivized organ and tissue donation. And establishment bioethics has caused preventable harm. Most infamous is the case of Jesse Gelsinger, the young man who died in a Phase-1 trial of gene therapy in 1999. Common sense would say that the experimental therapy should have been tested for safety on infants with a severe form of the disease who would have died anyway. But Arthur Caplan, the country’s most famous bioethicist, argued that the parents of such infants would be so consumed with grief that they could not truly give consent—the kind of paternalistic argument that is all too common in this field—and that an 18-year-old with a mild form of the disease, who technically could give consent, should be enrolled instead. A strained interpretation of the magic word “consent” was allowed to trump expected harm and benefit, and the result was tragedy.

There is, to be sure, an important role for bioethics. Satel puts it well: bioethicists at their best are “scholars who study the intellectual and social history of value controversies in medicine and biotechnology. They can teach us about the technical and cultural antecedents of modern debates and show us how to engage in disciplined moral inquiry. They are skilled at drawing conceptual maps of the dilemma at hand while enumerating various ways to resolve it.”

Knoepfler. 2. Forgetting bioethicists entirely for the moment, prominent scientists such as Jennifer Doudna, David Baltimore, and others have publicly called in unambiguous terms for at least a temporary moratorium on clinical applications of human germline editing technology. Do you disagree or agree? Why?

Pinker: Disagree. The specific harms they warn against, such as inducing cancer, mutations, or birth defects in the unborn child are already ruled out by a plethora of existing regulations and norms. Obviously we shouldn’t mess around with embryos in ways that have a significant probability of producing a sick or deformed child with no compensating benefit. But why do we need a new, across-the-board ban on an entire method to rule out what’s already ruled out on the uncontroversial grounds of protecting individuals against foreseeable harm? The authors seem to be acquiescing to the yuck-factor that surrounds the very idea of germline modification, if for no other reason than to draw a firewall around their own research programs, which are restricted to the genetic modification of somatic cells. But scientists should work to dismantle irrational taboos, not indulge them.

First, the idea that there is some sacrosanct entity called “the human germline,” such that deliberately manipulating it would violate this sanctity, or restrict the freedom of future generations, or alter the species in unprecedented and frightening ways, is biological nonsense. No two people, not even monozygotic twins, have the same germline. Each of us introduces dozens of random mutations into our germlines, often multiplied by voluntary choices such as exposing ourselves to mutagens like tobacco smoke or fathering a child in middle age. And we affect the genetic makeup of our offspring, and the species, every time we choose to have unprotected sex with one partner rather than another. So even if it did come to pass that some people edited out disease genes, or (far less likely—see below) edited in enhancement genes, it would be a droplet in the maelstrom of naturally churning genomes.

Second, a ban or moratorium would only reinforce the pernicious aura of dread that surrounds genomic modifications. This is the dread that incites across-the-board opposition to genetically modified organisms and that underpins the bogus moral arguments against cytoplasmic donation for mitochondrial disease (the so-called three-parent babies—another case in which so-called bioethical concerns increase rather than decrease death and suffering). And the spurious ideal of germline sacredness could compromise the treatment of disease in other ways. Though lots of things went wrong in the Gelsinger case, one complication was the decision to administer massive doses of the viral vector directly to his liver, with the risk of lethal inflammation, rather than systemically, out of the fear that (God forbid!) it might introduce the needed gene into his sperm-forming cells. That’s probably not what killed Gelsinger, but it did kill a monkey in a safety trial, and this germlinophobia could certainly endanger gene-therapy patients in the future.

Third, germline editing could have direct benefits in a number of scenarios: to parents with disease genes who don’t produce enough viable embryos for preimplantation genetic diagnosis (especially when more than one such gene is involved, which multiplies the number of necessary embryos); to parents who both are homozygous for some recessive disease gene (not far-fetched given how often people meet each other through support groups); if future data were to show that PGD babies have compromised longevity or health; and in other scenarios that perhaps we can’t imagine. For these reasons Savulescu, with Chris Gyngell, and Henry Miller with Drew Kershen argue that research on germline editing is not only morally permissible but morally imperative.

Knoepfler. 3. You appear relatively confident in future benefits of new biotechnology such as CRISPR to millions of people, but you seem very skeptical of the risk predictions that you described as “speculative harms”. What makes you so confident of benefit and at the same time so skeptical of risks? If us humans struggle generally at accurately predicting outcomes of biomedical science, why should there be a more accurate expectation of benefits as opposed to risks?

Pinker: No, this is wrong. Though it’s certain that the biomedical research enterprise as a whole will deliver benefits to billions of people, we can have no such confidence in particular technologies. That’s why we need a diversified research portfolio, without arbitrary bans. If you ban something, the probability that people will benefit is zero. If you don’t ban it, the probability is greater than zero.

As for the potential harms, they are far too nebulous to justify a ban or moratorium. Far from being confident in the power of gene editing, I’m on the record as being skeptical that we’ll ever see genetic enhancement of babies—the outcome that the prohibitionists and moratoristas dread and that many bioethicists blithely assume is inevitable. (For example, in 1999 Caplan announced that before the end of this century “We will see many children made by the artificial creation of embryos…This prediction is 100 percent certain.”) The prophesy of designer babies ought to be a relic of the early 1990s, when people thought there was “A Gene For” this or that talent. We now know that heritable psychological traits such as intelligence and personality are the product of hundreds or thousands of genes, each with a tiny effect, many of which may have harmful effects as well, such as an increased risk of neurological disease or cancer. With each enhancement gene providing a nugatory benefit and a non-negligible risk, and with the editing process itself imposing risks, it’s unlikely that today’s morbidly risk-averse helicopter parents will take a chance at enhancing a child—they won’t even feed their babies genetically modified applesauce! And that’s assuming that such a procedure ever got to the point of clearing conventional safety hurdles, which is far from likely. Add these risks to the fantastic expense and tribulation of IVF compared to good old-fashioned sex, and one should conclude that widespread genetic enhancement is too unlikely a possibility to worry about. And that’s assuming we should worry at all. There is, in addition, the argument (from Savulescu, the transhumanists, and others) that if enhancement were ever feasible it would be a good thing, not a bad thing—or at least a matter of individual freedom rather than government coercion.

Now, the story is different for editing out disease genes. There are more ways that a complex system can break down than that it can work better, and it’s easier to fix a defect than engineer in an improvement. Also, the benefits are very different for preventing death and disease (huge) than for implementing an enhancement (minor). So the possibility that germ-line editing might prevent disease in the future is well worth exploring.

Knoepfler. 4. Congress recently held a public hearing on human germline modification and is considering a legal provision to block editing of human embryos. What do you think of having such a hearing and the possibility of a restrictive legal provision? You said to bioethics, “get out of the way”. Should we scientists say the same thing to lawmakers? Why?

Knoepfler. 5. There is likely to be a NAS meeting sometime late this year on human germline modification by such technology as CRISPR-Cas9 and mitochondrial transfer (3-person IVF) in the spirit of the 1975 Asilomar meeting. Do you think this new meeting will achieve positive outcomes such as a white paper that appropriately has a vision for the future? What if the consensus is for a moratorium? Could you support that?

Pinker: I’ll answer these together. I think that scientists should reiterate the principle that no experiment should be permitted which imposes an unreasonable risk of an illness or birth defect on an individual. But no, I don’t think that scientists should support a ban or moratorium on germline genetic editing, for the reasons I set out in my answers to questions 2 and 3. Though the Asilomar recommendations have long been a source of self-congratulation among scientists, they were opposed by a number of geneticists at the time, who correctly argued that they were an overreaction which would needlessly encumber and delay important research. And the journalist Victor McElheny reminds us that the recommendations sowed a panic which came perilously close to shutting down some of the nation’s major laboratories, a danger he argues we are now in danger of repeating.

That having been said, I recognize that the political arena follows different rules than scientific and intellectual discourse. The scientists who lead major research institutions and deal with politicians and other public figures have to master the arts of compromise, tact, euphemism, and strategic deal-cutting. That’s how democracy works, and I’m grateful to the scientific leaders who carve out a space in which the rest of us can flourish. There are things they may believe but can’t say. But it’s important that someone says them, and that’s how I see my role in these debates.

15 Comments

“You hardly need a bioethicist to tell you that it’s wrong to […] withhold antibiotics from syphilis patients.”

But yet, this was in fact done, in the not too distant past. Why are safeguards not now needed, when their absence was tragic not very long ago?

If the argument is for “more gas, fewer brakes” — exactly how is the gas to be supplied in such a way as to avoid such atrocity? Surely the argument is not that the suffering of a few is justified by benefit of many…

“[…]an obvious ethical principle that life is better than death[…]”

Not every case of “a life worth having” is “a life worth [artificially] prolonging”.

There are various other straw men and deficiencies in the commentary.

In general, to examine only potential benefits but no potential drawbacks of biomedical research is to ignore the perpetually-flawed understanding scientists have of the fields they study. Beyond that, consider the behaviors often documented on Retraction Watch (particularly in the stem cell field).

Disease, death, and other hardships have always been and will always be with us, no matter how far science advances. Independent of scientific or technological development, we have always been free to care for each other or not, in life and when illness arrives and when death draws near — a moral undertaking worthy of serious consideration in its own right.

We are all diminished by the carelessness exhibited by anyone towards anyone else, of any age or circumstance.

Let us not use the omelet-requires-broken-eggs analogy to justify our experimentation on each other in the name of the future. Rather, let the future record a history of our steadfast mutual compassion and care even during our thorough and meticulous advancement of science and technology.

“You’d think it would be an obvious ethical principle that life is better than death” which seems to suggest that Pinker is poking his nose where it has no business to be (that is, not knowing what his is talking about). There are serious debates about assisted suicide, which according to Pinker, must be fundamentally misguided. But some clearly thinks that a painless suicide now is better than a painful death later (that is, death being better than life). And those of us that own or have owned a pet knows that death may be the ethical thing in some cases. But according to Pinker, we are deluded.

Furthermore, Pinker seems to think that we are horrible at predicting things (hard to argue with that) with apparently only when it comes to unfavourable outcomes: research should be dome because it will surely lead to good things, but never stopped or delayed because we think it will have dire consequences, because in theatre case we are probably wrong (never mind that we are often wrong in the first case as well).

Thanks Paul for posting this. The problem with the format is that he is allowed to voice his view point without being called on some major blunders. Just to mention one: He makes it sound as if our germline is constantly evolving by accumulating mutations. However, our genome has evolved to suppress mutations very efficiently by DNA repair mechanism of a fascinating variety. Only these mechanisms allows us to reach our life span, and that is why mutations in these systems are so deleterious.

“But yet, this was in fact done, in the not too distant past. Why are safeguards not now needed, when their absence was tragic not very long ago?”

Do you mean that not very long ago antibiotics were in fact held from syphilis patients? I was not aware of that. Can you provide references for further information?

“Surely the argument is not that the suffering of a few is justified by benefit of many…”

I believe you might be attributing beliefs to Pinker which he does not hold. Maybe you could provide some plausible argument in favour of your attribution.

“Not every case of “a life worth having” is “a life worth [artificially] prolonging”.

Of course. I took Pinker’s statement to mean that “ceteris paribus” to be alive is better than to die. I believe my interpretation is correct based on the following observations: A. Pinker is not an idiot B. whatever exception I may come up with has certainly occurred to him first.

“Disease, death, and other hardships have always been and will always be with us, no matter how far science advances.”

That’s an assumption for which you cannot possibly provide supporting evidence; in other words, it’s a statement of faith and as such irrelevant to the real world.

“Let us not use the omelet-requires-broken-eggs analogy to justify our experimentation on each other in the name of the future.”

I fully agree. Let’s not do that. Though I fail to see where Pinker has said anything remotely supporting it.

@Thomas:

“However, our genome has evolved to suppress mutations very efficiently by DNA repair mechanism of a fascinating variety.”

Tell that to cancer patients. I’m sure they will be relieved to learn that they cannot possibly suffer from cancer because their DNA just wouldn’t allow it.

i agree with pinker on tissue and organ donation. the reaction from the transplant ethicists is very revealing and reinforces his point about them being obstructionists at best because of fairness issues overriding saving people’s lives.

“However, our genome has evolved to suppress mutations very efficiently by DNA repair mechanism of a fascinating variety.”
Tell that to cancer patients. I’m sure they will be relieved to learn that they cannot possibly suffer from cancer because their DNA just wouldn’t allow it.

Efficiency of DNA repair cannot be disputed. Estimates of somatic mutation rates are about 120,000 errors per cell division. Without repair (well over 99% of errors are corrected) and a highly efficient immune system to detect emerging aberrations, an individual would accumulate so many errors in critical genes that the incidence of cancer would be around 100% soon after birth.

This is no consolation for cancer patients, but your statement has no factual framework and attempts (rather poorly) to be sensationalist. Are you Steven Pinker?

Bravo! Bravo! Bravo! Drs Pinker and Knoepfler. Some wonderful clarity on this important subject. As someone who has fought against the “bioethical” nonsense for 30 years in Assisted Reproduction, this comes as a breath of fresh air. You still see Caplan and others quoted, lauded and given a forum after what has been a consistent history of specious, error-filled gobbledegook standing firmly in the way of the very concrete needs of patients and the advancement of science and humanity.